Why do natural peptides vanish in minutes?
Your blood is full of enzymes (proteases) that cut peptide bonds, and small peptides get filtered out by the kidneys.
Natural GLP-1 lasts about 2 minutes — the enzyme DPP-4 clips it and switches it off.
Semaglutide was engineered to survive:
1️⃣ One amino acid swapped (Aib) so DPP-4 can't cut it
2️⃣ A fatty-acid tail that binds albumin, so the kidneys can't clear it quickly
Result: a half-life of about one week.
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Sources:
• Lau J, et al. "Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide." Journal of Medicinal Chemistry, 2015.
• Holst JJ. "The Physiology of Glucagon-like Peptide 1." Physiological Reviews, 2007.